Involvement of transient receptor potential canonical 1 (TRPC1) in angiotensin II-induced vascular smooth muscle cell hypertrophy
Involvement of transient receptor potential canonical 1 (TRPC1) in angiotensin II-induced vascular smooth muscle cell hypertrophy
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DOI：
10.1016/j.atherosclerosis.2006.12.033
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发表时间：
2007-12-01
期刊：
影响因子：
5.3
通讯作者：
Ito, Hiroshi
中科院分区：
文献类型：
--
作者：
Takahashi, Yoichiro;Watanabe, Hiroyuki;Ito, Hiroshi
血管紧张素 II (Ang II) 诱导血管平滑肌细胞 (VSMC) 肥大，这是导致动脉粥样硬化的主要事件之一。 Ca2+ 进入增加是 VSMC 肥大的重要刺激因素，但与 Ang 11 的关联仍有待确定。瞬时受体电位规范 1 (TRPC1) 形成钙池操纵的 Ca2+ (SOC) 通道，参与 Ca2+ 稳态。我们的目的是确定 TRPC1 在 Ang II 诱导的 VSMC 肥大中的潜在作用。为此，我们使用了培养的人冠状动脉平滑肌细胞（hCASMC）。 Ang II 诱导的肥大细胞中钙池操纵的 Ca2+ 进入 (SOCE) 增加，SOC 通道阻滞剂抑制 Ang II 诱导的肥大反应。尽管 hCASMC 持续表达 TRPC1、C3、C4、C5 和 C6，但只有 TRPC1 响应 Ang II 刺激而增加。 TRPC1 siRNA 降低 SOCE 并防止 Ang II 诱导的肥大。我们在人类 TRPC1 基因的 5 调控区发现了 NF-κ B 结合位点。电泳迁移率变动分析表明，Ang II 增加了 TRPC1 启动子的 NF-κ B 结合活性。与 NF-κ B 诱饵寡核苷酸共同治疗不仅降低了 TRPC1 表达，而且抑制了肥大反应。总之，我们的数据表明，Ang II 和随后的 NF-κ B 激活通过增强 TRPC1 表达诱导 hCASMC 肥大。 (C) 2007 Elsevier Ireland Ltd. 保留所有权利。
Angiotensin II (Ang II) induces vascular smooth muscle cell (VSMC) hypertrophy as one of the major events leading to atherosclerosis. Increased Ca2+ entry is an important stimulus for VSMC hypertrophy, but the association with Ang 11 remains to be determined. Transient receptor potential canonical 1 (TRPC1) forms store-operated Ca2+ (SOC) channels that are involved in Ca2+ homeostasis. Our aim was to ascertain the potential involvement of TRPC1 in Ang II-induced VSMC hypertrophy. For this purpose, we used cultured human coronary artery smooth muscle cells (hCASMCs). Store-operated Ca2+ entry (SOCE) increased in the Ang II-induced hypertrophied cells, and SOC channel blocker inhibited the Ang II-induced hypertrophic response. Although hCASMCs constitutively expressed TRPC1, C3, C4, C5, and C6, only TRPC1 increased in response to Ang II stimulation. TRPC1 siRNA decreased SOCE and prevented Ang II-induced hypertrophy. We found NF-kappa B binding sites in the 5-regulatory region of the human TRPC1 gene. An electrophoretic mobility shift assay showed that Ang II increased the TRPC1 promoter's NF-kappa B binding activity. Co-treatment with NF-kappa B decoy oligonucleotides not only reduced TRPC1 expression, but also inhibited the hypertrophic responses. In conclusion, our data suggest that Ang II and subsequent NF-kappa B activation induces hCASMC hypertrophy through an enhancement of TRPC1 expression. (C) 2007 Elsevier Ireland Ltd. All rights reserved.